1. Field of the Invention
The present invention relates generally to the fields of cell biology and drug delivery. Particularly, it concerns the use of inactivated or modified toxins to deliver drugs to the cytoplasm of target cells
2. Description of Related Art
New therapies are under development that seek to address diseased states at the molecular level. A major problem in the practical application of many new therapeutic agents is that the agents do not readily cross cellular membranes and thus cannot reach compartments within the cell where their sites of action may reside. There are numerous reasons why agents are unable to penetrate cell membranes including the intrinsic charge, size, and chemical composition of the agents. Potentially therapeutic molecules such as nucleic acids, oligonucleotides, proteins, peptides and other related agents, as well as a small organic compounds, are subject to these limitations.
Prior art methods facilitate the passage of some of these agents across membranes, but the methods are usually not highly efficient nor are they readily applied to an intact organism, or both. Moreover, they are not usually able to deliver material selectively to a desired cell type by specifically binding to features of the desired target cell. For example, the passage of nucleic acids across a membrane and into cells can be facilitated by methods such as electroporation, calcium phosphate precipitation, and liposome-mediated transfection and attachment to facilitating peptides. These methods often are membrane disruptive and damage cells, limiting their effectiveness in vivo, or are not able to specifically deliver to desired target cells.